This application has six goals. The first is to overproduce T3Rs in mammalian cells and develop methods for their purification. The second is to characterize the biochemical properties of the receptors, including their specific affinities for each other, for T3, and for various DNA binding sites. The third is to characterize the in vivo regulatory properties of the various T3R types using a recently developed quantitative transfection system. The fourth is to characterize the interactions between the ligand binding domains of the T3Rs genetically. The fifth is to use the purified receptors to develop in vitro transcription systems responsive to both their negative or positive regulatory effects. The sixth is to investigate the interactions of the purified receptors with other proteins of the nuclear hormone receptor superfamily.